Ocular complications of diabetes are major causes of blindness in adults of the industrialized countries. The hyperglycemia of diabetes induces increased aldose reductase activity and accumulation of polyol in tissues that do not require insulin or glucose uptake. This section has been actively involved in studies of the potential use of aldose reductase inhibitors (ARIs) in ameliorating corneal, lenticular, and retinal lesions related to hyperglycemia. Both intervention soon after the earliest ultrastructural lesions could be documented as well as prevention initiated before tissue damage develops have demonstrated efficacy of various potent ARIs in lowering tissue polyol and ameliorating cataracts and diabetic retinopathy. Recently this section has demonstrated, for the first time, a diabetic-like loss of corneal sensitivity in the galactose-fed rat model of ocular complications. Experiments are under way to determine how soon the first functional changes occur, if they correlate with alterations in innervation patterns of nerve ultrastructure, and if such hexose-induced corneal damages can be halted, delayed, or reversed by intervention with ARIs. Although ARIs appear to be efficacious in the retina, the precise mechanism remains obscure because: (1) galactosemia increases the levels of nonenzymatic glycosylation as well as tissue polyol; (2) there is no current method to measure either polyol or glycation levels in the retinal pericytes, where the earliest damage occurs; and (3) it is not clear whether the levels in blood and/or the whole retina provide adequate surrogates. Because both polyol and glycation levels can be measured in the lens epithelium, where the first ultrastructural changes occur, we plan to initiate studies to distinguish the relative roles of nonenzymatic glycosylation as well as tissue polyol in diabetic cataracts.